This invention relates to novel aminobenzosultam derivatives and their use. The compounds of the present invention inhibit the action of lipoxygenase enzyme and are useful in the treatment or alleviation of inflammatory diseases, allergy and cardiovascular diseases in mammals. This invention also relates to pharmaceutical compositions comprising such compounds.
Arachidonic acid is known to be the biological precursor of several groups of endogenous metabolites, prostaglandins including prostacyclins, thrombaxanes and leukotrienes. The first step of the arachidonic acid metabolism is the release of arachidonic acid and related unsaturated fatty acids from membrane phospholipids, via the action of the phospholipase. Free fatty acids are then metabolized either by cyclooxygenase to produce the prostaglandins and thromboxanes or by lipoxygenase to generate hydroperoxy fatty acids which may be further converted to the leukotrienes.
Leukotrienes have been implicated in the pathophysiology of inflammatory disease, including rheumatoid arthritis, gout, asthma, ischemia reperfusion injury, psoriasis and inflammatory bowel disease. Any drug that inhibits lipoxygenase is expected to provide significant new therapy for both acute and chronic inflammatory conditions.
Recently several review articles on lipoxygenase inhibitors have been reported. (See H. Masamune and L. S. Melvin, Sr., in: Annual Reports in Medicinal Chemistry 24 (1989) pp71-80 (Academic), B. J. Fitzsimmons and J. Rokach in: Leukotrienes and Lipoxygenases (1989) pp 427-502 (Elsevier).
References which relate to benzosultams include U.S. Pat. Nos. 3,539,584, 3,303,190 and 3,177,221, Japanese Patent 4359/68 and Japanese Patent Application (kokai) 61470/89.